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Aneuploidy-associated gene expression signatures characterize malignant transformation in ulcerative colitis

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Aneuploidy-associated gene expression signatures characterize malignant transformation in ulcerative colitis. / Gerling, Marco; Nousiainen, Kari; Hautaniemi, Sampsa; Krüger, Stefan; Fritzsche, Britta; Homann, Nils; Bruch, Hans-Peter; Auer, Gert; Roblick, Uwe J; Ried, Thomas; Habermann, Jens K.

In: INFLAMM BOWEL DIS, Vol. 19, No. 4, 05.03.2013, p. 691-703.

Research output: SCORING: Contribution to journal › SCORING: Journal article › Research

Harvard

Gerling, M, Nousiainen, K, Hautaniemi, S, Krüger, S, Fritzsche, B, Homann, N, Bruch, H-P, Auer, G, Roblick, UJ, Ried, T & Habermann, JK 2013, 'Aneuploidy-associated gene expression signatures characterize malignant transformation in ulcerative colitis', INFLAMM BOWEL DIS, vol. 19, no. 4, pp. 691-703. https://doi.org/10.1097/MIB.0b013e31827eeaa4

APA

Gerling, M., Nousiainen, K., Hautaniemi, S., Krüger, S., Fritzsche, B., Homann, N., Bruch, H-P., Auer, G., Roblick, U. J., Ried, T., & Habermann, J. K. (2013). Aneuploidy-associated gene expression signatures characterize malignant transformation in ulcerative colitis. INFLAMM BOWEL DIS, 19(4), 691-703. https://doi.org/10.1097/MIB.0b013e31827eeaa4

Vancouver

Gerling M, Nousiainen K, Hautaniemi S, Krüger S, Fritzsche B, Homann N et al. Aneuploidy-associated gene expression signatures characterize malignant transformation in ulcerative colitis. INFLAMM BOWEL DIS. 2013 Mar 5;19(4):691-703. https://doi.org/10.1097/MIB.0b013e31827eeaa4

Bibtex

@article{b0fac29013c14bb29761a5e0e06576d6,
title = "Aneuploidy-associated gene expression signatures characterize malignant transformation in ulcerative colitis",
abstract = "BACKGROUND: Malignant transformation in ulcerative colitis (UC) is associated with pronounced chromosomal instability, reflected by aneuploidy. Although aneuploidy can precede primary cancer diagnosis in UC for more than a decade, little is known of its cellular consequences.METHODS: Whole-genome gene expression analysis was applied to noninflamed colon mucosa, mucosal biopsies of patients with UC, and UC-associated carcinomas (UCCs). DNA image cytometry was used to stratify samples into ploidy types. Differentially expressed genes (DEGs) were analyzed by Ingenuity Pathway Analysis and validated by real-time quantitative PCR.RESULTS: Gene expression changes were more pronounced between normal mucosa and UC (2587 DEGs) than between UC and UCC (827 DEGs). Cytometry identified colitis patients with euploid or aneuploid mucosa biopsies, whereas all UCCs were aneuploid. However, 1749 DEGs distinguished euploid UC and UCCs, whereas only 15 DEGs differentiated aneuploid UC and UCCs. A total of 16 genes were differentially expressed throughout the whole sequence from normal controls to UCCs. Particularly, genes pivotal for chromosome segregation (e.g., SMC3 and NUF2) were differentially regulated along aneuploidy development.CONCLUSIONS: The high number of DEGs between normal mucosa and colitis is dominated by inflammatory-associated genes. Subsequent acquisition of aneuploidy leads to subtle but distinct transcriptional alterations, revealing novel target genes that drive genomic instability and thus carcinogenesis. The gene expression signature of malignant phenotypes in aneuploid UC suggests that these lesions might need to be considered as severe as high-grade dysplasia.",
keywords = "Adult, Aged, Aneuploidy, Biomarkers, Tumor, Cell Transformation, Neoplastic, Colitis, Ulcerative, Colonic Neoplasms, Female, Gene Expression Profiling, Genomic Instability, Humans, Intestinal Mucosa, Male, Middle Aged, Oligonucleotide Array Sequence Analysis, Precancerous Conditions, Prognosis, RNA, Messenger, Real-Time Polymerase Chain Reaction, Reverse Transcriptase Polymerase Chain Reaction, Journal Article, Research Support, Non-U.S. Gov't",
author = "Marco Gerling and Kari Nousiainen and Sampsa Hautaniemi and Stefan Kr{\"u}ger and Britta Fritzsche and Nils Homann and Hans-Peter Bruch and Gert Auer and Roblick, {Uwe J} and Thomas Ried and Habermann, {Jens K}",
year = "2013",
month = mar,
day = "5",
doi = "10.1097/MIB.0b013e31827eeaa4",
language = "English",
volume = "19",
pages = "691--703",
journal = "INFLAMM BOWEL DIS",
issn = "1078-0998",
publisher = "John Wiley and Sons Inc.",
number = "4",

}

RIS

TY - JOUR

T1 - Aneuploidy-associated gene expression signatures characterize malignant transformation in ulcerative colitis

AU - Gerling, Marco

AU - Nousiainen, Kari

AU - Hautaniemi, Sampsa

AU - Krüger, Stefan

AU - Fritzsche, Britta

AU - Homann, Nils

AU - Bruch, Hans-Peter

AU - Auer, Gert

AU - Roblick, Uwe J

AU - Ried, Thomas

AU - Habermann, Jens K

PY - 2013/3/5

Y1 - 2013/3/5

N2 - BACKGROUND: Malignant transformation in ulcerative colitis (UC) is associated with pronounced chromosomal instability, reflected by aneuploidy. Although aneuploidy can precede primary cancer diagnosis in UC for more than a decade, little is known of its cellular consequences.METHODS: Whole-genome gene expression analysis was applied to noninflamed colon mucosa, mucosal biopsies of patients with UC, and UC-associated carcinomas (UCCs). DNA image cytometry was used to stratify samples into ploidy types. Differentially expressed genes (DEGs) were analyzed by Ingenuity Pathway Analysis and validated by real-time quantitative PCR.RESULTS: Gene expression changes were more pronounced between normal mucosa and UC (2587 DEGs) than between UC and UCC (827 DEGs). Cytometry identified colitis patients with euploid or aneuploid mucosa biopsies, whereas all UCCs were aneuploid. However, 1749 DEGs distinguished euploid UC and UCCs, whereas only 15 DEGs differentiated aneuploid UC and UCCs. A total of 16 genes were differentially expressed throughout the whole sequence from normal controls to UCCs. Particularly, genes pivotal for chromosome segregation (e.g., SMC3 and NUF2) were differentially regulated along aneuploidy development.CONCLUSIONS: The high number of DEGs between normal mucosa and colitis is dominated by inflammatory-associated genes. Subsequent acquisition of aneuploidy leads to subtle but distinct transcriptional alterations, revealing novel target genes that drive genomic instability and thus carcinogenesis. The gene expression signature of malignant phenotypes in aneuploid UC suggests that these lesions might need to be considered as severe as high-grade dysplasia.

AB - BACKGROUND: Malignant transformation in ulcerative colitis (UC) is associated with pronounced chromosomal instability, reflected by aneuploidy. Although aneuploidy can precede primary cancer diagnosis in UC for more than a decade, little is known of its cellular consequences.METHODS: Whole-genome gene expression analysis was applied to noninflamed colon mucosa, mucosal biopsies of patients with UC, and UC-associated carcinomas (UCCs). DNA image cytometry was used to stratify samples into ploidy types. Differentially expressed genes (DEGs) were analyzed by Ingenuity Pathway Analysis and validated by real-time quantitative PCR.RESULTS: Gene expression changes were more pronounced between normal mucosa and UC (2587 DEGs) than between UC and UCC (827 DEGs). Cytometry identified colitis patients with euploid or aneuploid mucosa biopsies, whereas all UCCs were aneuploid. However, 1749 DEGs distinguished euploid UC and UCCs, whereas only 15 DEGs differentiated aneuploid UC and UCCs. A total of 16 genes were differentially expressed throughout the whole sequence from normal controls to UCCs. Particularly, genes pivotal for chromosome segregation (e.g., SMC3 and NUF2) were differentially regulated along aneuploidy development.CONCLUSIONS: The high number of DEGs between normal mucosa and colitis is dominated by inflammatory-associated genes. Subsequent acquisition of aneuploidy leads to subtle but distinct transcriptional alterations, revealing novel target genes that drive genomic instability and thus carcinogenesis. The gene expression signature of malignant phenotypes in aneuploid UC suggests that these lesions might need to be considered as severe as high-grade dysplasia.

KW - Adult

KW - Aged

KW - Aneuploidy

KW - Biomarkers, Tumor

KW - Cell Transformation, Neoplastic

KW - Colitis, Ulcerative

KW - Colonic Neoplasms

KW - Female

KW - Gene Expression Profiling

KW - Genomic Instability

KW - Humans

KW - Intestinal Mucosa

KW - Male

KW - Middle Aged

KW - Oligonucleotide Array Sequence Analysis

KW - Precancerous Conditions

KW - Prognosis

KW - RNA, Messenger

KW - Real-Time Polymerase Chain Reaction

KW - Reverse Transcriptase Polymerase Chain Reaction

KW - Journal Article

KW - Research Support, Non-U.S. Gov't

U2 - 10.1097/MIB.0b013e31827eeaa4

DO - 10.1097/MIB.0b013e31827eeaa4

M3 - SCORING: Journal article

C2 - 23455720

VL - 19

SP - 691

EP - 703

JO - INFLAMM BOWEL DIS

JF - INFLAMM BOWEL DIS

SN - 1078-0998

IS - 4

ER -